Association between soluble suppression of tumorigenicity 2 and risk and severity of coronary artery disease: a case control study

Abstract

Background: To investigate the differential expression of soluble suppression of tumorigenicity 2 (sST2) in patients with coronary artery disease (CAD) and healthy controls, and the correlation between sST2 and the severity of coronary artery atherosclerosis.

Methods: A total of 911 CAD patients were selected as the CAD group, and 322 healthy people were selected as the control group. We measured serum sST2 level by chemiluminescence immunoassay, and applied the Gensini scoring system to quantify the severity of coronary artery atherosclerosis. We utilized Mann-Whitney U test to assess the difference of sST2 level between the two groups, and adopted Spearman correlation test to evaluate the correlation between sST2 level and Gensini score and inflammatory indexes.

Results: Compared with the control group, the expression level of sST2 in CAD group was significantly increased [29.20 (20.67, 46.34) vs. 19.69 (15.97, 25.02), P < 0.001]. Logistic regression showed that sST2 expression could increase CAD risk (OR = 1.099, 95%CI: 1.080 ~ 1.119, P < 0.001). Analysis of variance revealed that the sST2 expression level increased gradually in unstable angina pectoris group (UA), non-ST elevation myocardial infarction group (NSTEMI) and ST elevation myocardial infarction group (STEMI) [UA: 23.05 (17.54, 30.75), NSTEMI: 30.71 (21.31, 42.97), STEMI: 51.05 (32.85, 80.04), P < 0.001]. Spearman correlation analysis demonstrated significantly positive associations between sST2 expression level and Gensini score (r = 0.137, P < 0.001), and systemic inflammatory indexes MHR (r = 0.188, P < 0.001), NLR (r = 0.469, P < 0.001), PLR (r = 0.285, P < 0.001) and MLR (r = 0.368, P < 0.001), but negatively correlated with AFR (r=-0.135, P < 0.001). By receiver operating characteristic (ROC) curve analysis, the sST2 expression level had excellent predictive effect in STEMI with the area under the curve (AUC) value of 0.926 (95%CI: 0.903-0.948, P < 0.001) and sensitivity and specificity of 72.3% and 99.7% respectively, superior to NSTEMI with an AUC of 0.760 (95%CI: 0.719-0.802, P < 0.001) and UA with an AUC of 0.616 (95%CI: 0.576-0.656, P < 0.001).

Conclusions: sST2 could not only serve as a biomarker for the clinical auxiliary diagnosis of CAD, but also act as a potential indicator for disease progression or risk stratification. Dynamic monitoring of sST2 levels might assist in evaluating treatment efficacy.

Keywords: Coronary artery disease; Inflammatory index; Soluble suppression of tumorigenicity 2; sST2.

Fig. 1

sST2 expression levels in different groups. (A). Comparison of sST2 expression levels between the control group and CAD group analyzed by Mann-Whitney U test. (B). Comparison of sST2 expression levels across the control group, unstable angina (UA) group, non-ST-segment elevation myocardial infarction (NSTEMI) group and ST-segment elevation myocardial infarction (STEMI) group analyzed by analysis of variance (ANOVA)

Fig. 2

Expression and association of sST2. (A). Correlation of sST2 expression level with the Gensini score analyzed by Spearman correlation test. (B). Comparison of sST2 expression levels between the mild and severe stenosis group analyzed by Mann-Whitney U test

Fig. 3

Correlations of sST2 expression level with inflammatory indexes analyzed by Spearman correlation test. sST2 expression level was positively correlated with the Monocyte to High-density Lipoprotein Ratio (MHR, r = 0.188, A), the Neutrophil to Lymphocyte Ratio (NLR, r = 0.469, B), the Platelet to Lymphocyte Ratio (PLR, r = 0.285, C), the Monocyte to Lymphocyte Ratio (MLR, r = 0.368, D), and negatively correlated with the Albumin to Fibrinogen Ratio (AFR, r=-0.135, E)

Fig. 4

Receiver operating characteristic (ROC) curve analyses of sST2 in predicting coronary artery disease (CAD) (A), unstable angina (UA) (B), non-ST-segment elevation myocardial infarction (NSTEMI) (C) and ST-segment elevation myocardial infarction (STEMI) (D)